Affective disorders remain the most common of the disabling psychiatric illnesses. However, as we examine the expression of these disorders across the adult lifespan, it becomes obvious that there are multiple pathways into and out of illness. Over the next five years, the MHCRC for Affective Disorders at the University of Pittsburgh will continue to encourage multiple approaches to the study of affective disorders. Organizing ail of these approaches is the assumption that depression involves a dysfunction of numerous, interrelated systems and not simply a change of mood. The attempt to understand these interrelationships creates bridges across investigations of psychopathology therapeutics, regulatory systems, and molecular genetics. The Department of Psychiatry (WPIC), in collaboration with other departments within the School of Medicine and the Faculty of Arts and Sciences at the University of Pittsburgh, at Carnegie Mellon University and at other research centers across the country, will continue to investigate the etiology, pathophysiology, course and treatment of affective disorders. The MHCRC provides the essential organizational structure and core support for our integrated, multidisciplinary program of research and research training. The cores required to support the next five years of research activities are: l) Administrative and Data Management Core, 2) Diagnostic and Therapeutics Evaluation Core, 3) Psychobiology Core, 4) Clinical Psychopharmacology Core, and 5) the Methodology Core. These five core support systems provide common facilities, technical expertise and scientific direction, integrating the work of a large number of research scientists. In addition, the MHCRC will permit continued seed funding of young investigators, the pairing of seasoned investigators with these young scientists and communication among the senior faculty interested in widely differing aspects of affective disorders. Clinical research programs, are organized around the themes of recurrent disorders, psychosocial factors, and regulatory disturbances, as viewed through a longitudinal perspective and as altered by treatment interventions. Research programs focussed on basic biologic rhythms complement our major commitment to clinical psychobiology and therapeutics for affective disorders.